Abstract
Per- and polyfluoroalkyl substances (PFAS) are widespread environmental pollutants with documented developmental toxicity. Prior research of prenatal PFAS exposure and offspring neurodevelopment did not consider the possible influence from paternal exposure. Using the INUENDO cohort, we studied 334 father-mother-singleton triads enrolled from antenatal clinics in Greenland, Poland, and Ukraine. We measured five PFAS in parental serum samples collected around the 31 weeks of gestation. We assessed child behavioral difficulties at ages 5-9 years by the parent-rated Strength and Difficulties Questionnaire using country- and sex-specific cut-offs (≥90th percentile). We performed analyses stratified by child's sex, coadjusting for maternal or paternal PFAS and other confounders and estimating PFAS mixture effects using quantile g-computation. In male children, multiple maternal PFAS, modeled as individual chemicals or a mixture, were associated with externalizing difficulties. Maternal perfluorononanoic acid (PFNA) was associated with internalizing difficulties in female children. In contrast, paternal exposure to individual PFAS or PFAS mixture was not associated with behavioral difficulties in children of either sex. In summary, maternal prenatal exposure to PFAS, but not paternal PFAS, was associated with mid-childhood behavioral difficulties in a sex-specific manner. Comparing the parent-specific PFAS associations strengthened evidence against confounding shared in the family.